The perfect vascular graft for arterial reconstructive surgery remains to be developed. The inherent thrombognicity of currently available prostheetic grafts and the inadequacies of the fibrin coagulum that forms as an interface between the artificial conduit and circulating blood restricts their use to large vessels. Since the only truly non-thrombogenic material known is the endothelium of natural vessels, this project seeks to isolate these and other cells, seed then into artificial vascular prostheses during surgical procedures and thus provide a non-thrombogenic living cellular interface between blood and graft. We have previously described methods to accomplish this goal and now propose to refine and expand upon them including the determination of: (a) the optimal method of seeding, (b) the fate of the seeded cells within the graft, (c) the number of cells necessary and their relation to the rate of healing, (d) the effect of seeding combinations of endothelium, smooth muscle and fibroblasts and (e) the effectiveness of the cellular lining in preventing graft infection. After the development of methods for human endothelial cells have been completed, preliminary clinical studies will begin on seeded angio-access, femoro-femoral, femoro-popliteal and axillo-femoral grafts in human patients. In order to assess the functional role of the cellular linings, studies of III in labelled platelet turnover and scintiscanning of grafts, threshold dose aggregometry, platelet serotonin and beta thromboglobulin, and PgI(2) activity of the lining cells will be undertaken. The data from these studies will be correlated with the morphology of the graft surface to relate endothelial cell coverage and healing to function.